DESCRIPTION: BALB/c mice are more susceptible than C57BL/6 mice to radiation-induced instability and it is hypothesized that this difference determines transformation frequency differences in the two mouse strains. Analysis of F1 progeny suggests that the difference in susceptibility for induction of mammary cancer is a heritable trait and Preliminary Data suggests a similar pattern for inheritance of susceptibility to the induction of cytogenetic instability. Experiments are proposed which will: 1) use F1 and F2 progeny of BALB/c and C57BL/6 mice to determine the pattern of inheritance for susceptibility to genetic instability and radiation transformation; 2) use these recombinant inbred strains to examine co-segregation of the loci controlling the phenotypic traits; and 3) map the loci that determine the susceptibility differences. It is hoped that mapping of these loci will ultimately lead to cloning of the involved genes. Identification of such genes should help identify pathways mechanistically involved in the induction of instability and transformation and may be useful in identifying sub-populations of people who are at increased risk for radiation-induced cancer.